The possibility that rheumatoid arthritis (RA) may be caused by viral infection of synovial or lymphoid tissues will be investigated. Organ and cell cultures of normal and RA synovium will be examined for the presence of specific antigen or evidence of viral infection. We will search for a specific antigen by assaying for cell mediated immune (CMI) reactivity of lymphocytes from RA patients for their own and allogenic synovial tissues. Methods used will include assay for cytotoxicity by Cr51 release, blastogenic lymphocyte response, and the production of soluble mediators of CMI by the macrophage migration inhibition assay. Our search for evidence of viral infection of RA synovial and lymphoid tissues will utilize assays for metabolic, biochemical or functional changes in RA cells which are suggestive of viral infection. Tests used will include assay for RNA directed DNA polymerase as a marker of oncorna virus infection, and DNA directed polymerase as evidence of DNA virus infection.